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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study determined whether the beneficial effects of exercise training on the diabetic heart previously observed are associated with alterations in ventricular myosin heavy chain (MHC) isoform composition. Diabetes was induced in rats by i.v. streptozotocin. Trained rats were run on a treadmill for 60 min/day, 27 m/min, 10% grade. After 10 wks, ventricular MHC isoenzyme protein composition was analyzed for MHC composition using gel electrophoresis. alpha-MHC and beta-MHC mRNA were determined by Northern and slot blot hybridization techniques. Both protein and mRNA analyses indicated that sedentary control rats exhibited a predominance of alpha-MHC. Sedentary diabetics exhibited a shift to beta-MHC. Exercise trained diabetic rats showed a predominance of beta-MHC. The results indicate that treadmill exercise training of diabetic rat does not prevent the diabetes-induced shift in MHC composition towards the beta-MHC isoform, thus it is unlikely that the beneficial effects of exercise training on the diabetic heart, previously shown, are due to a normalization of the myosin isoform composition.
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PMID:Effects of exercise training and diabetes on cardiac myosin heavy chain composition. 148 51

Epidemiological studies have clearly shown that the so-called metabolic syndrome which is linked to insulin resistance and a reduced glucose utilization of muscle represents an important risk factor for cardiovascular disease. However, only little is known of the intracellular consequences of insulin resistance. An important feature of an altered substrate utilization is related to signal transduction of gene expression. For the example of myosin heavy chain expression, it is shown that metabolic signals exist which reflect the fuel flux and substrate utilization of the heart muscle cell. The signals were characterized in functional states of the heart associated with altered metabolic influences (fasting, diabetes, sucrose feeding, increased calorie intake, carnitine palmitoyltransferase inhibition). In the pressure-overloaded heart, metabolic interventions which are expected to increase glucose utilization (sucrose feeding, captopril treatment) have a pronounced effect. Although a link with gene expression remains to be established, it should be noted that the sarcoplasmic reticulum Ca(2+)-pump activity seems to be affected in a functionally comparable manner. It is concluded that metabolic signals alter the protein phenotype of heart muscle and it is expected that a deranged signal transduction affects, not only the heart, but also vascular muscle.
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PMID:The metabolic syndrome and signal transduction of gene expression. 183 54

In the rat heart diabetes mellitus leads to a change in myosin heavy chain (MHC) mRNAs and corresponding alterations in myosin isoenzymes as well as a decrease in total cardiac protein synthesis. However, it is still unknown whether cardiac proteins other than MHC are altered by diabetes and if so whether these abnormalities are mediated by insulin deficiency. To answer these questions we analyzed proteins synthesized by isolated cardiac myocytes in the presence or absence of insulin. Enzymatically dispersed adult cardiac myocytes from control and streptozotocin-induced diabetic rats were incubated in medium containing [35S]-methionine for 4 h; diabetic cells were incubated with or without the addition of 5 x 10(-7)M insulin. The labelled peptides were then separated by two-dimensional polyacrylamide gel electrophoresis and analyzed by fluorometry. The abundance of six individual polypeptides was consistently affected by diabetes: one protein was significantly decreased while four others were increased in diabetic myocytes. The remaining protein showed a shift in isoelectric point without a change in molecular weight possibly representing isoforms of a single polypeptide. The addition of insulin reverted the predominance of three proteins back to normal while it did not affect the other three at all. In conclusion diabetes induces changes in the abundance of a few proteins synthesized in vitro by cardiac myocytes and only half of them show an acute response to insulin.
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PMID:Diabetes-induced changes of proteins synthesized by adult cardiac myocytes are partially reversed by insulin. 306 85

In diabetes a primary myocardial defect occurs that is characterized by decreases in systolic pressure and cardiac output. The present study investigates whether diabetes causes a decreased maximum tension-generating ability, decreased Ca2+ sensitivity of myofilaments, or no change in cardiac myofilament contractile properties at pH 7.0 and 6.6. Hearts from Wistar rats were excised and mechanically disrupted 6-10 wk after injection of streptozotocin. The resulting myocyte-size preparations of skinned myocardium were used to determine the steady-state tension-negative, log molar Ca2+ concentration (pCa) relation. Maximum tension was unchanged, and the pCa of half-maximum tension generation was 0.14 pCa units lower than control for skinned myocytes from diabetic rats at pH 7.0. A significantly lower than normal maximum tension was observed at pH 6.6 for cardiac myocytes from diabetic rats. Increased expression of beta-myosin heavy chain (MHC) occurred in hearts from diabetic rats. Two troponin T (TnT) isoforms in myocardium of adult rats were identified by Western blots. The ratio of the two TnT isoforms were altered in diabetes. Changes in cardiac MHC and TnT expression may contribute to the observed decrease in Ca2+ sensitivity of myofilaments at pH 7.0 and decreased maximum tension-generating ability at pH 6.6 in diabetes.
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PMID:Effects of diabetes on isometric tension as a function of [Ca2+] and pH in rat skinned cardiac myocytes. 750 62

The severity and frequency of atherosclerosis, diabetes, and ischemic heart disease, which affect cardiac function, increase with aging. Although there are many reports about hemodynamic and histopathological studies about aging hearts, there are very few studies on changes in structural proteins in aging hearts. We investigated the contractile proteins of the left ventricles in rats aged 6, 12 and 125 weeks using two-dimensional electrophoresis. There were no difference in structural proteins in heart between 6-week and 12-week-old rats. The contents of myosin heavy chain, myosin light chain 2, actin, troponin-I in 125-week-old rats decreased compared with those of 12-week-old rats. Myosin heavy chain, which is one component of myosin, interacts with actin and changes chemical energy to mechanical energy. Therefore its decrease leads to a decline in myocardial contractility. These results seem to indicate one of the most important changes in the aging rat heart, as well as impairment in relaxation by the increase of interstitial fibrosis and decline of Ca uptake by sarcoplasmic reticulum.
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PMID:[Analysis by two-dimensional electrophoresis of the cause of myocardial dysfunction in aging rat hearts]. 836 Oct 80

Our group has documented that myocardial performance is impaired in the hearts of chronically diabetic rats and rabbits. Abnormalities in the contractile proteins and regulatory proteins may be responsible for the mechanical defects in the streptozotocin (STZ)-diabetic hearts. Previously, the major focus of our research on contractile proteins in abnormal states has concentrated on myosin ATPase and its isoenzymes. Our present study is based on the overall hypothesis that regulatory proteins, in addition to contractile protein, myosin contribute to altered cardiac contractile performance in the rat model of diabetic cardiomyopathy. The purpose of our research was to define the role of cardiac regulatory proteins (troponin-tropomyosin) in the regulation of actomyosin system in diabetic cardiomyopathy. For baseline data, myofibrillar ATPase studies were conducted in the myofibrils from control and diabetic rats. To focus on the regulatory proteins (troponin and tropomyosin), individual proteins of the cardiac system were reconstituted under controlled conditions. By this approach, myosin plus actin and troponin-tropomyosin from the normal and diabetic animals could be studied enzymatically. The proteins were isolated from the cardiac muscle of control and STZ-diabetic (4 weeks) rats. Sodium dodecyl sulfate gel electrophoretic patterns demonstrate differences in the cardiac TnT and TnI regions of diabetic animals suggesting the different amounts of TnT and/or TnI or possibly different cardiac isozymes in the regulatory protein complex. Myofibrils probed with a monoclonal antibody TnI-1 (specific for adult cardiac TnI) show a downregulation of cardiac TnI in diabetics when compared to its controls. Enzymatic data confirm a diminished calcium sensitivity in the regulation of the cardiac actomyosin system when regulatory protein(s) complex was recombined from diabetic hearts. Actomyosin ATPase activity in the hearts of diabetic animals was partially reversed when myosin from diabetic rats was regulated with the regulatory protein complex isolated from control hearts. To our knowledge, this is the first study which demonstrates that the regulatory proteins from normal hearts can upregulate cardiac myosin isolated from a pathologic rat model of diabetes. This diminished calcium sensitivity along with shifts in cardiac myosin heavy chain (V1-->V3) may be partially responsible for the impaired cardiac function in the hearts of chronic diabetic rats.
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PMID:Troponin subunits contribute to altered myosin ATPase activity in diabetic cardiomyopathy. 856 62

Diabetes is known to alter the myosin phenotype of striated muscle, but the impact of the same diabetic state on different types of striated muscles remains unknown. Therefore, this study determined the myosin isoenzyme profile in the left ventricle, soleus, plantaris, and extensor digitorium longus (EDL) of young male rats made moderately diabetic with streptozotocin, (45 mg/kg, ip). Eight weeks after the single streptozotocin injection, tissues were collected and subsequently electrophoretically analyzed for native myosin isoenzyme distribution. Skeletal muscles were additionally analyzed for myosin heavy chain distribution. Neither the native myosin isoform nor the myosin heavy chain (MHC) distribution profiles of the skeletal muscles were altered by the diabetic state. In contrast, the high ATPase cardiac isoform, VI, was significantly replaced by the low ATPase isoform, V3 (p < 0.05). These results demonstrate that striated muscle responds to a moderate diabetic state in a limited and muscle specific fashion. Significantly, the change in the cardiac myosin isoform profile is comparable to that which occurs in a more severe diabetic state.
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PMID:Morderate diabetes alters myosin isoenzyme distribution in cardiac but not skeletal muscle of male rats. 860 16

The phenotypic change of the mesangial cell is considered to play a pivotal role in the accumulation of extracellular matrix in diabetic nephropathy. This investigation was undertaken to evaluate the expression of the various isoforms of contractile proteins in the streptozocin (STZ)-induced diabetic rat kidney and in renal biopsy specimens from patients with diabetic nephropathy. Specific antibodies to myosin heavy chain isoforms (SM1, SM2, SMemb), caldesmon, and alpha-smooth muscle actin and cDNAs for SMemb were used. Increased expression of SMemb at the mRNA and protein levels was demonstrated at 1 week after STZ administration in the rat. Both levels were increased at 4 weeks. Mesangial staining of caldesmon was observed at 4 weeks and that of alpha-smooth muscle actin at 24 weeks. Immunohistochemical mesangial staining of the contractile proteins was pronounced in patients with diabetic nephropathy in contrast to the trace mesangial staining in normal control subjects. These results indicate that the phenotypic change in mesangial cells occurs in the early stages of diabetes and that several stages in phenotypic changes may exist. Expression of the contractile protein isoforms, especially SMemb, should serve as a new marker for the subsequent glomerular hypertrophy and sclerosis.
Diabetes 1996 Apr
PMID:Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. 860 71

To characterize the phenotypic modulation of mesangial and glomerular epithelial cells, we investigated the expression of a nonmuscle type myosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in rat experimental glomerular diseases, which included anti-Thy 1 nephritis, 5/6 nephrectomy, diabetes, and anti-glomerular basement membrane nephritis. SMemb was only slightly expressed in normal glomerular epithelial cells but not in mesangial cells. In the anti-Thy 1 nephritis rats, both SMemb and alpha-SM actin were most conspicuously induced in mesangial cells. However, the expression profile was shifted from alpha-SM actin to SMemb dominant pattern over the course of glomerulonephritis. The expression of SMemb was also increased in epithelial cells in this model. In the other three models, glomerular cells did not express alpha-SM actin, but did so for SMemb. In the nephrectomized and the diabetic rats SMemb was newly expressed in mesangial cells at earlier stages, but at later stages was remarkably enhanced in epithelial cells when severe glomerular hypertrophy developed. In the anti-GBM nephritis rats, SMemb expression was increased in epithelial cells. In all models examined, mesangial and epithelial expression of SMemb was confirmed by immunoelectron microscopy, and enhanced expression of SMemb mRNA in glomeruli was verified by RNase protection assay. We conclude from these results that glomerular cells change their phenotypes differently depending on various types of glomerular diseases. These phenotypic changes in glomerular cells can be revealed by the combined immunostaining for SMemb and alpha-SM actin. SMemb is especially useful to detect both mesangial and glomerular epithelial cell activation in these glomerular disease models. Understanding the functional difference and regulatory mechanisms of these cytoskeletal proteins will provide insight into the pathogenesis and progression of glomerular diseases.
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PMID:Expression of a nonmuscle myosin heavy chain in glomerular cells differentiates various types of glomerular disease in rats. 873 Oct 86

To characterize the molecular mechanism of cardiac and renal complications in non-insulin-dependent diabetes mellitus (NIDDM), we examined the gene expression of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new animal model for human NIDDM, at the ages of 14 weeks (prediabetic stage), 30 weeks (NIDDM stage), and 54 weeks (IDDM stage). Tissue mRNA levels were measured by Northern blot analysis. In 14-week-old OLETF rats, cardiac mRNAs for transforming growth factor-beta1 (TGF-beta1) and extracellular matrix, including collagen types I, III, and IV and laminin, were significantly increased compared with control rats (Long-Evans Tokushima Otsuka rats). Cardiac beta-myosin heavy chain (MHC) mRNA of OLETF was increased at 30 and 54 weeks of age, whereas alpha-MHC mRNA of OLETF was inversely decreased at 54 weeks. Marked perivascular fibrosis was seen in the hearts of OLETF rats from 30 weeks of age. In the kidney of OLETF rats, glomerular TGF-beta1 expression was temporally increased at 30 weeks of age, followed by glomerulosclerosis characterized by mesangial proliferation, thickening of the basement membrane, and nodular lesions. Blood pressure of OLETF rats remained higher than that of control rats from the prediabetic stage to the IDDM stage. Thus, in OLETF rats, cardiac fibrosis-related gene expressions were already enhanced at the prediabetic stage, which supports the involvement of these gene expressions in cardiac perivascular fibrosis. The antithetical change in beta- and alpha-MHC expressions seems to participate in the decreased cardiac contractility seen in diabetes. Furthermore, TGF-beta1 may also contribute to glomerulosclerosis of OLETF rats. OLETF rats seem to be a useful model to study the mechanism of hypertension and cardiac and renal complications in NIDDM.
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PMID:Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fatty rats. 905 88


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